Listeriosis is an infectious disease caused by the intracellular bacterium Listeria monocytogenes. To control the infection effectively, the host immune response is directed by intercellular signalling molecules called cytokines that are produced by immune cells following sensing of the bacteria. In this study we used gene expression analysis to examine complex immune signalling networks in the blood and tissues of mice infected with L. monocytogenes. We show that a large set of genes are perturbed in both blood and tissue upon infection and that the transcriptional responses in both are enriched for pathways of the immune response. From these data we also observe an important signalling network emerge from a group of cytokines called interferons (IFNs). Previous findings suggest that different IFN family members can determine the balance between successful and impaired immune responses to L. monocytogenes and several other bacterial infections. Using mice deficient for the detrimental type I IFN signalling pathway we show that IFN-inducible genes are differentially regulated at different times upon infection but also present at much lower levels in uninfected mice highlighting how dysregulation of this network in the steady state may determine the outcome of this bacterial infection.
Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.
Sex, Specimen part, Treatment
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TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Specimen part
View SamplesAnalysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 2]
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Specimen part
View SamplesAnalysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 1]
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Specimen part
View SamplesExpression of meningioma 1 (MN1) has been proposed to be a negative prognostic molecular marker in adult AML with normal cytogenetics, however its role in pediatric leukemia is unknown. We found elevated MN1 expression in 53 of 88 pediatric leukemia cases: significant amounts of MN1 were found in immature B-cell ALL and most cases of infant leukemia but no MN1 expression was detected in T-cell acute lymphoblastic leukemia (T-ALL). Interestingly 17 of 19 cases harboring MLL-X fusions showed also elevated MN1 expression. Lentiviral siRNA mediated MN1 knock-down resulted in cell cycle arrest and impaired clonogenic growth of 3 MLL-X-positive human leukemia cell lines overexpressing MN1 (THP-1, RS4;11, MOLM13). In a mouse MLL/ENL-induced leukemia MN1 overexpression resulted from retroviral provirus insertion. Strikingly co-expression of MN1 with MLL/ENL resulted in significantly reduced latency for induction of an AML phenotype in mice suggesting functional cooperation. MN1 overexpression in MLL/ENL-carrying cells resulted in expansion of the L-GMP population and facilitated disease induction in secondary recipients. Gene expression profiling allowed to define a number of potential MN1 hematopoietic targets. Up-regulation of CD34, FLT3, HLF, or DLK1 was validated in bone marrow transiently overexpressing MN1, in MN1-induced mouse leukemias, as well as in some cases of pediatric leukemias overexpressing MN1. Taken together, our work suggests that MN1 overexpression is essential for growth of leukemic cells, and that MN1 can act as a cooperating oncogene with MLL-X fusion genes most probably through modification of a distinct gene expression program that leads to expansion of a leukemia initiating cell population.
Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia.
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View SamplesEstrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced myeloproliferative neoplasm in vivo, and sensitized MLL-AF9+ leukemias to chemotherapy. Tamoxifen showed selective effects on mutant cells compared to normal ones, and had only a minor impact on steady-state hematopoiesis in disease-free animals. These results uncover specific regulation of hematopoietic progenitors by estrogens and potential anti-leukemic properties of SERM Overall design: LT-HSCs, ST-HSCs and MPPs sorted from the bone marrow of mice treated with tamoxifen or vehicle (3 biological replicates per group)
Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis.
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Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
Sex, Specimen part
View SamplesCharacterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
No sample metadata fields
View SamplesCharacterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.
Specimen part
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